Study on the synergistic effect and mechanism of curcumin combined with zerumbone on the biological behavior of non-small cell lung cancer cells / 中国药房

OBJECTIVE To investigate the synergistic effect and mechanism of curcumin （CUR） combined with zerumbone （ZER） on the biological behavior of non-small cell lung cancer （NSCLC） A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group， CUR group， ZER group， and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis， and clone formation experiment was used to evaluate cell proliferation ability， scratch experiment and Transwell migration experiment were used to evaluate cell migration ability， and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase （p- PI3K）， phosphorylated protein kinase B （p-Akt）， and vascular endothelial growth factor A （VEGF-A）. RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L， respectively； the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index， with the cell proliferation inhibition rate of （77.41±4.16）%， indicating the most significant synergistic effect. Compared with the CUR and ZER groups， the cell apoptosis rate in the CUR+ZER group was significantly increased （P＜0.01）， while the cell clone formation rate， cell migration rate， the number of migrating cells， the number of invading cells， and relative expression levels of p-PI3K， p-Akt， and VEGF-A proteins in the cells were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The combination of CUR and ZER has a synergistic effect， significantly promoting the apoptosis of NSCLC cells， and inhibiting cell proliferation， migration， and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway， thereby down-regulating the protein expression of VEGF-A.

Incidence and Risk Factors for Radiotherapy-Induced Oral Mucositis Among Patients With Nasopharyngeal Carcinoma: A Meta-Analysis

Purpose@#To evaluate the incidence and identify the risk factors for radiotherapy-induced oral mucositis among patients with nasopharyngeal carcinoma. @*Methods@#A meta-analysis was conducted. Eight electronic databases (Medline, Embase, Cochrane Library, CINAHL Plus with Full Text, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journals Database) were systematically searched from inception to 4 March 2023 for relevant studies. Study selection and data extraction were conducted by two independent authors. The Newcastle‒Ottawa scale was used for quality assessment among the included studies. Data synthesis and analyses were performed in R software package version 4.1.3 and Review Manager Software 5.4. The pooled incidence was calculated using proportions with 95% confidence intervals (CIs), and the risk factors were evaluated using the odds ratio (OR) with 95% CIs. Sensitivity analysis and predesigned subgroup analyses were also conducted. @*Results@#A total of 22 studies published from 2005 to 2023 were included. The results of the meta-analysis showed that the incidence of radiotherapy-induced oral mucositis was 99.0% among nasopharyngeal carcinoma patients, and the incidence of severe radiotherapy-induced oral mucositis was 52.0%. Poor oral hygiene, overweight before radiotherapy, oral pH < 7.0, the use of oral mucosal protective agents, smoking, drinking, combined chemotherapy, and the use of antibiotics at early treatment stage are risk factors for severe radiotherapy-induced oral mucositis. Sensitivity analysis and subgroup analyses also revealed that our results are stable and reliable. @*Conclusions@#Almost all patients with nasopharyngeal carcinoma have suffered from radiotherapy-induced oral mucositis, and more than half of patients have experienced severe oral mucositis. Facilitating oral health might be the key focus of reducing the incidence and severity of radiotherapy-induced oral mucositis among nasopharyngeal carcinoma patients.Registration numberCRD42022322035.

Radix Panacis quinquefolii Extract Ameliorates Inflammatory Bowel Disease through Inhibiting Inflammation / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD).@*METHODS@#The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction.@*RESULTS@#Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01).@*CONCLUSION@#RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

Research Progress of Iron Metabolism in Disease Progression and Drug Resistance of Multiple Myeloma--Review / 中国实验血液学杂志

Iron metabolism is involved in the development and drug resistance of many malignancies, including multiple myeloma (MM). Based on recent studies on iron metabolism and MM, this paper reviews the relationship between iron metabolism and disease process of MM in terms of iron overload leading to ferroptosis in MM cells, the role of iron deficiency in oxidative respiration and proliferation of MM cells, and the interaction between ferroptosis and autophagy in the disease process. The mechanisms by which iron metabolism-related substances lead to MM cells' resistance to proteasome inhibitors (PI) through inducing redox imbalance and M2 macrophage polarization are also briefly described, aiming to provide a theoretical basis for the application of iron metabolism-related drugs to the clinical treatment of MM patients.

Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children.@*METHODS@#School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables.@*RESULTS@#Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status.@*CONCLUSION@#Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.

Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC / 中国肺癌杂志

BACKGROUND@#Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients.@*METHODS@#66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored.@*RESULTS@#The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life.@*CONCLUSIONS@#Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.

Effect of Raw and Bran-fried Atractylodis Rhizoma on Protein Carriers Related to Small Intestinal Absorption Transport in Spleen Deficiency Rats / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of bran-fried Atractylodis Rhizoma （AR） in improving gastrointestinal function by comparing the effects of raw AR and bran-fried AR on the small intestine tissue structure and transport-related protein carriers in rats with spleen deficiency syndrome. MethodSeventy male SD rats were randomly divided into a normal group， a model group， high- and low-dose raw AR groups （10， 2.5 g·kg-1）， high- and low-dose bran-fried AR groups （10， 2.5 g·kg-1）， and a compound glutamine group （9 mg·kg-1）， with 10 rats in each group. Except for the normal group， the other six groups were subjected to the spleen deficiency model induced by the method of bitter and cold breaking stagnated Qi and abnormal hunger and fullness for 21 days. After modeling， each treatment group was given medication orally according to the corresponding doses every day for a total of 14 days， and the normal group and the model group were given an equal volume of normal saline orally. During the treatment period， the general survival status， macroscopic syndrome score， daily increase in body weight and food intake， and rectal temperature of the spleen deficiency rats were evaluated， and after the treatment， the rats were sacrificed. The pathological changes in the small intestine tissues of each group were observed by hematoxylin-eosin （HE） staining. The content of serum 5-hydroxytryptamine （5-HT） was detected by enzyme-linked immunosorbent assay （ELISA）， and the content of serum D-xylose， lactate， and amylase was detected by colorimetry. The levels of free fatty acid receptor 3 （FFA3） and peptide transporter 1 （PepT1） in small intestinal tissues were detected by the Bradford method， and the protein expression of sodium-dependent glucose transporter 1 （SGLT1） and glucose transporter 1 （GLUT1） in small intestinal tissue was detected by immunohistochemistry. Real-time fluorescence-based quantitative PCR was used to detect the mRNA expression of glucose transporter 2 （GLUT2）， sodium/hydrogen exchanger 3 （NHE3）， and 5-hydroxytryptamine receptor 4 （5-HT4R）. ResultCompared with the normal group， the model group exhibited symptoms of spleen deficiency， such as sluggishness， squint， reduced food intake， and lethargy at the end of modelling， damaged basic structure of the small intestinal mucosal epithelium and lamina propria， increased serum lactate and 5-HT content， and decreased serum amylase and D-xylose （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement， with the small intestinal microstructure repaired to different degrees. The daily weight gain， anal temperature， and macroscopic syndrome score of spleen deficiency improved to varying degrees （P<0.05， P<0.01）. The serum lactate and 5-HT content decreased to varying degrees， while the serum amylase and D-xylose content increased to varying degrees （P<0.05， P<0.01）. The PepT1 content in the small intestinal tissues increased， while the FFA3 content decreased to varying degrees. The protein expression of SGLT1 and GLUT1 increased， while the mRNA expression of GLUT2 and NHE3 increased to varying degrees. The mRNA expression of 5-HT4R decreased to varying degrees （P<0.05， P<0.01）. Compared with the high- and low-dose raw AR groups， the high- and low-dose bran-fried AR groups showed significant improvement in general conditions and histopathological improvement of the small intestinal tissues. The daily weight gain， anal temperature， and macroscopic syndrome score of spleen deficiency also improved （P<0.05， P<0.01）. The serum lactate and 5-HT content decreased， while the serum amylase and D-xylose content increased （P<0.05， P<0.01）. The PepT1 content in the small intestinal tissues increased， while the FFA3 content decreased. The protein expression of SGLT1 and GLUT1 increased， while the mRNA expression of GLUT2 and NHE3 increased. The mRNA expression of 5-HT4R decreased significantly （P<0.05， P<0.01）. ConclusionBran-fried AR can improve the spleen deficiency-related symptoms and histopathology of the small intestinal tissues in spleen deficiency model rats. Its mechanism may be related to the regulation of the expression of various transport-related protein carriers and the secretion of various digestive enzymes after stir-frying of AR， thus restoring the absorption and transport function of the small intestine.

Pathogenesis and surgical outcomes of different types of myopic traction maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P&#x003C;0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P&#x003C;0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P&#x003C;0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P&#x003C;0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P&#x003C;0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish.@*METHODS@#The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe.@*RESULTS@#The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae.@*CONCLUSION@#KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Automatic determination of mandibular landmarks based on three-dimensional mandibular average model / 北京大学学报(医学版)

OBJECTIVE@#To explore an efficient and automatic method for determining the anatomical landmarks of three-dimensional(3D) mandibular data, and to preliminarily evaluate the performance of the method.@*METHODS@#The CT data of 40 patients with normal craniofacial morphology were collected (among them, 30 cases were used to establish the 3D mandibular average model, and 10 cases were used as test datasets to validate the performance of this method in determining the mandibular landmarks), and the 3D mandibular data were reconstructed in Mimics software. Among the 40 cases of mandibular data after the 3D reconstruction, 30 cases that were more similar to the mean value of Chinese mandibular features were selected, and the size of the mandibular data of 30 cases was normalized based on the Procrustes analysis algorithm in MATLAB software. Then, in the Geomagic Wrap software, the 3D mandibular average shape model of the above 30 mandibular data was constructed. Through symmetry processing, curvature sampling, index marking and other processing procedures, a 3D mandible structured template with 18 996 semi-landmarks and 19 indexed mandibular anatomical landmarks were constructed. The open source non-rigid registration algorithm program Meshmonk was used to match the 3D mandible template constructed above with the tested patient's 3D mandible data through non-rigid deformation, and 19 anatomical landmark positions of the patient's 3D mandible data were obtained. The accuracy of the research method was evaluated by comparing the distance error of the landmarks manually marked by stomatological experts with the landmarks marked by the method of this research.@*RESULTS@#The method of this study was applied to the data of 10 patients with normal mandibular morphology. The average distance error of 19 landmarks was 1.42 mm, of which the minimum errors were the apex of the coracoid process [right: (1.01±0.44) mm; left: (0.56±0.14) mm] and maximum errors were the anterior edge of the lowest point of anterior ramus [right: (2.52±0.95) mm; left: (2.57±1.10) mm], the average distance error of the midline landmarks was (1.15±0.60) mm, and the average distance error of the bilateral landmarks was (1.51±0.67) mm.@*CONCLUSION@#The automatic determination method of 3D mandibular anatomical landmarks based on 3D mandibular average shape model and non-rigid registration algorithm established in this study can effectively improve the efficiency of automatic labeling of 3D mandibular data features. The automatic determination of anatomical landmarks can basically meet the needs of oral clinical applications, and the labeling effect of deformed mandible data needs to be further tested.

Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants.@*METHODS@#China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP).@*RESULTS@#A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05).@*CONCLUSIONS@#Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Analysis of teaching difficulties in the chapter of antigen in Medical Immunology and teaching strategy / 细胞与分子免疫学杂志

The concept of "ntigen"is a relative one. The narrow concept of it condenses the process of activation of adaptive immune response and re-recognition of the same antigen, revealing the protective mechanism of vaccines with great significance for research and development of vaccines. However, the narrow concept involves adaptive immune system members: B cells, T cells and their effector products, which is difficult for beginners to understand the inherent meaning. Meanwhile, antigen classification fully summarizes the immune response process, so a variety of classification approach increases the difficulty in learning. Our teaching team analyzes the difficulties of this chapter in depth, and we implements the strategy that takes antibody structure and function as the breakthrough point and simplified adaptive immune response process as the core in teaching. A mind map that includes the main contents of this chapter is made during the process, which promotes the effectiveness of classroom teaching greatly.

Distribution of monocyte subsets and their surface CD31 intensity are associated with disease course and severity of hemorrhagic fever with renal syndrome / 细胞与分子免疫学杂志

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14++CD16-), intermediated monocyte subsets (CD14++CD16+) and non-classical monocyte subsets (CD14+CD16++) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers / 中国中药杂志

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, β-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Application of Deep Learning in Differential Diagnosis of Ameloblastoma and Odontogenic Keratocyst Based on Panoramic Radiographs / 中国医学科学院学报

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

The design method of the digital sequential tooth-sectioning guide for the extraction of mandibular impacted third molars / 中华口腔医学杂志

Objective: To explore a method for digitally designing and fabricating a sequential tooth-sectioning guide that can assist in the extraction of mandibular horizontal impacted third molars, preliminarily evaluate its feasibility and provide a reference for clinical application. Methods: Twenty patients with mandibular low level impacted third molars who visited the Department of General Dentistry, Peking University School and Hospital of Stomatology from March 2021 to January 2022 were selected. Cone-beam CT showed direct contact between the roots and mandibular canal, and full range impressions of the patients' intraoral teeth were taken and optical scans of the dental model were performed. The patients' cone-beam CT data and optical scan data were reconstructed in three dimensions, anatomical structure extraction, registration fusion, and the design of the structure of the guide (including crown-sectioning guide and root-sectioning guide) by Mimics 24.0, Geomagic Wrap 2021, and Magics 21.0 software, and then the titanium guide was three dimension printed, and the guide was tried on the dental model. After confirmation, the guide was used to assist the dentist in the operation. We observed whether the guide was in place, the number of tooth splitting, the matching of tooth splitting with the preoperative design, the operation time, and whether there were any complications. Results: In this study, 20 sectioning guides were successfully printed, all of them were well fitted in the patients' mouth, the average number of section was 3.4 times, the tooth parts was better matched with the preoperative design, and the average operative time of the guides was (29.2±9.8) minutes without complications such as perforation of the bone cortex. Conclusions: The use of sequential sectioning guides to assist in the extraction of mandibular impacted third molars was initially validated to accurately replicate the preoperative sectioning design, and is expected to provide a digital solution to improve surgical precision and ensure safety. Further studies with larger sample sizes are needed to evaluate its accuracy and safety.

Analysis and prediction of thyroid cancer morbidity and mortality trends in China / 中华流行病学杂志

Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.

The relationship between classroom environment and myopia / 中华流行病学杂志

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m2 was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.